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Q8NAU1

- FNDC5_HUMAN

UniProt

Q8NAU1 - FNDC5_HUMAN

Protein

Fibronectin type III domain-containing protein 5

Gene

FNDC5

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
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    • History
      Entry version 105 (01 Oct 2014)
      Sequence version 3 (05 Sep 2012)
      Previous versions | rss
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    Functioni

    Irisin: Contrary to mouse, may not be involved in the beneficial effects of muscular exercise, nor in the induction of browning of human white adipose tissue.1 Publication

    GO - Biological processi

    1. positive regulation of brown fat cell differentiation Source: UniProtKB
    2. response to muscle activity Source: UniProtKB

    Keywords - Molecular functioni

    Hormone

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Fibronectin type III domain-containing protein 5
    Alternative name(s):
    Fibronectin type III repeat-containing protein 2
    Cleaved into the following chain:
    Gene namesi
    Name:FNDC5
    Synonyms:FRCP2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:20240. FNDC5.

    Subcellular locationi

    Cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication. Peroxisome membrane By similarity; Single-pass type I membrane protein By similarity
    Note: Imported in peroxisomes through the PEX5 receptor pathway.By similarity
    Chain Irisin : Secreted
    Note: Detected in the blood of individuals subjected to endurance exercise.1 Publication

    GO - Cellular componenti

    1. endoplasmic reticulum Source: UniProtKB
    2. extracellular region Source: UniProtKB
    3. integral component of membrane Source: UniProtKB-KW
    4. peroxisomal membrane Source: UniProtKB-SubCell
    5. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane, Peroxisome, Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134924607.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3131Sequence AnalysisAdd
    BLAST
    Chaini32 – 212181Fibronectin type III domain-containing protein 5PRO_0000328971Add
    BLAST
    Chaini32 – 143112IrisinPRO_0000415857Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi39 – 391N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi84 – 841N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    The extracellular domain is cleaved and released from the cell membrane.
    N-Glycosylated.By similarity

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    PaxDbiQ8NAU1.
    PRIDEiQ8NAU1.

    PTM databases

    PhosphoSiteiQ8NAU1.

    Expressioni

    Tissue specificityi

    Widely expressed, with highest levels in heart. Very low expression, if any, in colon, pancreas and spleen.1 Publication

    Inductioni

    Has been shown to be up-regulated some twofold by muscular exercise at the mRNA and protein level; this effect has been suggested to be mediated by PPARGC1A (PubMed:22237023). However, up-regulation upon exercise could not be reproduced, at least not at the mRNA level (PubMed:24040023).2 Publications

    Gene expression databases

    BgeeiQ8NAU1.
    CleanExiHS_FNDC5.
    GenevestigatoriQ8NAU1.

    Organism-specific databases

    HPAiHPA051290.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000362570.

    Structurei

    Secondary structure

    1
    212
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi38 – 447
    Beta strandi50 – 556
    Turni59 – 613
    Beta strandi62 – 7312
    Beta strandi77 – 848
    Beta strandi89 – 924
    Beta strandi100 – 11112
    Beta strandi120 – 1234

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4LSDX-ray2.28A/B/C/D/E/F/G/H33-130[»]
    ProteinModelPortaliQ8NAU1.
    SMRiQ8NAU1. Positions 33-130.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini32 – 152121ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini174 – 21239CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei153 – 17321HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini36 – 12792Fibronectin type-IIIPROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi210 – 2123Microbody targeting signalSequence Analysis

    Sequence similaritiesi

    Contains 1 fibronectin type-III domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG87775.
    HOGENOMiHOG000082536.
    HOVERGENiHBG067308.
    InParanoidiQ8NAU1.
    OMAiPDENGME.
    OrthoDBiEOG7S2206.
    TreeFamiTF325415.

    Family and domain databases

    Gene3Di2.60.40.10. 1 hit.
    InterProiIPR003961. Fibronectin_type3.
    IPR013783. Ig-like_fold.
    [Graphical view]
    PfamiPF00041. fn3. 1 hit.
    [Graphical view]
    SMARTiSM00060. FN3. 1 hit.
    [Graphical view]
    SUPFAMiSSF49265. SSF49265. 1 hit.
    PROSITEiPS50853. FN3. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8NAU1-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MHPGSPSAWP PRARAALRLW LGCVCFALVQ ADSPSAPVNV TVRHLKANSA    50
    VVSWDVLEDE VVIGFAISQQ KKDVRMLRFI QEVNTTTRSC ALWDLEEDTE 100
    YIVHVQAISI QGQSPASEPV LFKTPREAEK MASKNKDEVT MKEMGRNQQL 150
    RTGEVLIIVV VLFMWAGVIA LFCRQYDIIK DNEPNNNKEK TKSASETSTP 200
    EHQGGGLLRS KI 212
    Length:212
    Mass (Da):23,659
    Last modified:September 5, 2012 - v3
    Checksum:iC4A066452A05A134
    GO
    Isoform 2 (identifier: Q8NAU1-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         180-181: KD → EA
         182-212: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:181
    Mass (Da):20,281
    Checksum:i36BEE521AFABE5A6
    GO
    Isoform 3 (identifier: Q8NAU1-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-75: Missing.
         212-212: I → VRARPGPGWATLCLMLW

    Note: No experimental confirmation available.

    Show »
    Length:153
    Mass (Da):17,323
    Checksum:i4DA2ABEAC5B4D934
    GO
    Isoform 4 (identifier: Q8NAU1-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-75: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:137
    Mass (Da):15,527
    Checksum:i1045BF9CE29A41E4
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 7575Missing in isoform 3 and isoform 4. 2 PublicationsVSP_032860Add
    BLAST
    Alternative sequencei180 – 1812KD → EA in isoform 2. 1 PublicationVSP_032861
    Alternative sequencei182 – 21231Missing in isoform 2. 1 PublicationVSP_032862Add
    BLAST
    Alternative sequencei212 – 2121I → VRARPGPGWATLCLMLW in isoform 3. 1 PublicationVSP_032863

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK092102 mRNA. Translation: BAC03806.1.
    AC114493 Genomic DNA. No translation available.
    CH471059 Genomic DNA. Translation: EAX07499.1.
    CH471059 Genomic DNA. Translation: EAX07502.1.
    CH471059 Genomic DNA. Translation: EAX07500.1.
    BC062297 mRNA. Translation: AAH62297.1.
    BX537781 mRNA. Translation: CAD97840.1.
    BF221649 mRNA. No translation available.
    CCDSiCCDS369.2. [Q8NAU1-1]
    CCDS65483.1. [Q8NAU1-3]
    RefSeqiNP_001165411.2. NM_001171940.1. [Q8NAU1-2]
    NP_001165412.1. NM_001171941.2. [Q8NAU1-3]
    NP_715637.2. NM_153756.2. [Q8NAU1-1]
    UniGeneiHs.524234.

    Genome annotation databases

    EnsembliENST00000496770; ENSP00000476320; ENSG00000160097. [Q8NAU1-3]
    GeneIDi252995.
    KEGGihsa:252995.
    UCSCiuc001bwf.2. human. [Q8NAU1-1]
    uc001bwg.3. human. [Q8NAU1-3]

    Polymorphism databases

    DMDMi403314395.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK092102 mRNA. Translation: BAC03806.1 .
    AC114493 Genomic DNA. No translation available.
    CH471059 Genomic DNA. Translation: EAX07499.1 .
    CH471059 Genomic DNA. Translation: EAX07502.1 .
    CH471059 Genomic DNA. Translation: EAX07500.1 .
    BC062297 mRNA. Translation: AAH62297.1 .
    BX537781 mRNA. Translation: CAD97840.1 .
    BF221649 mRNA. No translation available.
    CCDSi CCDS369.2. [Q8NAU1-1 ]
    CCDS65483.1. [Q8NAU1-3 ]
    RefSeqi NP_001165411.2. NM_001171940.1. [Q8NAU1-2 ]
    NP_001165412.1. NM_001171941.2. [Q8NAU1-3 ]
    NP_715637.2. NM_153756.2. [Q8NAU1-1 ]
    UniGenei Hs.524234.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4LSD X-ray 2.28 A/B/C/D/E/F/G/H 33-130 [» ]
    ProteinModelPortali Q8NAU1.
    SMRi Q8NAU1. Positions 33-130.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000362570.

    PTM databases

    PhosphoSitei Q8NAU1.

    Polymorphism databases

    DMDMi 403314395.

    Proteomic databases

    PaxDbi Q8NAU1.
    PRIDEi Q8NAU1.

    Protocols and materials databases

    DNASUi 252995.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000496770 ; ENSP00000476320 ; ENSG00000160097 . [Q8NAU1-3 ]
    GeneIDi 252995.
    KEGGi hsa:252995.
    UCSCi uc001bwf.2. human. [Q8NAU1-1 ]
    uc001bwg.3. human. [Q8NAU1-3 ]

    Organism-specific databases

    CTDi 252995.
    GeneCardsi GC01M033327.
    HGNCi HGNC:20240. FNDC5.
    HPAi HPA051290.
    MIMi 611906. gene.
    neXtProti NX_Q8NAU1.
    PharmGKBi PA134924607.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG87775.
    HOGENOMi HOG000082536.
    HOVERGENi HBG067308.
    InParanoidi Q8NAU1.
    OMAi PDENGME.
    OrthoDBi EOG7S2206.
    TreeFami TF325415.

    Miscellaneous databases

    GenomeRNAii 252995.
    NextBioi 92038.
    PROi Q8NAU1.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q8NAU1.
    CleanExi HS_FNDC5.
    Genevestigatori Q8NAU1.

    Family and domain databases

    Gene3Di 2.60.40.10. 1 hit.
    InterProi IPR003961. Fibronectin_type3.
    IPR013783. Ig-like_fold.
    [Graphical view ]
    Pfami PF00041. fn3. 1 hit.
    [Graphical view ]
    SMARTi SM00060. FN3. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49265. SSF49265. 1 hit.
    PROSITEi PS50853. FN3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
    2. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
      Tissue: Brain.
    5. The Cancer Genome Anatomy Project (CGAP) at the National Cancer Institute
      Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-133 (ISOFORM 1).
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 20-212 (ISOFORM 2).
      Tissue: Fetal liver.
    7. Cited for: INDUCTION, SUBCELLULAR LOCATION.
    8. Cited for: FUNCTION, INDUCTION, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiFNDC5_HUMAN
    AccessioniPrimary (citable) accession number: Q8NAU1
    Secondary accession number(s): A6NMC9
    , D3DPQ6, Q6P6D9, Q7Z676
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 8, 2008
    Last sequence update: September 5, 2012
    Last modified: October 1, 2014
    This is version 105 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3